LipidsLipidsDr. Mamoun AhramNursingFirst semester, 2016

Types of lipidsTypes of lipids

Lipids are biomolecules which are soluble in organic non-polar solvents. Consequently, fats and lipids are insoluble in water. Lipids can be divided into different groups according to their structure and they include:

Fatty acidsGlycerides and waxesPhospholipids (glycerophospholipids and sphingolipids)GlycolipidsSteroidsEicosanoids

Lipids are not considered polymers since they are not made of distinct monomers like carbohydrates, proteins, and nucleic acids

Classification of lipidsClassification of lipids

Fatty acidsFatty acids

A fatty acid contains a long hydrocarbon chain and a terminal carboxylate groupThey have various lengths (number of carbons) and degrees of unsaturation (single and double bonds)

Amphipathic moleculesAmphipathic molecules

They are an excellent examples of amphipathic molecules (those that have a hydrophilic part-polar head-and a hydrophobic part-nonpolar tail)Another term if amphiphilic (Gk. amphi = both)

Types of fatty acidsTypes of fatty acids

Saturated fatty acids are those with all of C-C bonds being single.

Unsaturated fatty acids are those with one or more double bonds between carbonsMonounsaturated fatty acid:

a fatty acid containing one double bond.

Polyunsaturated fatty acids contain two or more double bonds.

Fatty acids-more infoFatty acids-more info

Fatty acids in biological systems usually contain an even number of carbon atoms, typically between 14 and 24The 16- and 18-carbon fatty acids are most common

Cis vs. trans bondsCis vs. trans bonds

The configuration of the double bonds in most unsaturated fatty acids is cis rather than in the trans position.note the difference in bond structure.

Designation of fatty acidsDesignation of fatty acids

The notation 16:0 denotes a C16 fatty acid with no double bonds such as palmitic acid, a C16 saturated fatty acid18:2 signifies that there are two double bonds such as the unsaturated C18 linoleic acidFatty acid carbon atoms are numbered starting at the carboxyl terminusThe position of a double bond is represented by the symbol Δ followed by a superscript number

cis-Δ9 means that there is a cis double bond between carbon atoms 9 and 10; trans-Δ2 means that there is a trans double bond between carbon atoms 2 and 3

Common fatty acidsCommon fatty acids

Number of carbons

Number of double bonds

Common name

140Myristate

160Palmitate

180Stearate

181Oleate

182Linoleate

183Linolenate

204Arachidonate

Another way of namingAnother way of naming

The methyl carbon atom at the distal end of the chain is called the omega (ω)-carbon atomSo, the position of a double bond can be denoted by counting from the distal end, with the ω-carbon atom (the methyl carbon) as number 1

Effect of double bondsEffect of double bonds

Unsaturated fatty acids have lower melting points than saturated fatty acids of the same lengthFor example, the melting point (Tm) of stearic acid is 69.6°C, whereas that of oleic acid (which contains one cis double bond) is 13.4°C

The properties of fatty acids are dependent on chain length and degree of saturation

Effect of chain lengthEffect of chain length

Chain length also affects the melting point, as illustrated by the fact that the melting temperature of palmitic acid (C16) is 6.5 degrees lower than that of stearic acid (C18)Thus, short chain length and unsaturation enhance the fluidity of fatty acids and of their derivatives

Essential fatty acidsEssential fatty acids

Polyunsaturated fatty acids such as linoleic acid and linolenic acid, are essential fatty acids, meaning that we cannot synthesize them in our bodies and we must get them from diet.

Deficiency of essential fatty acids in Deficiency of essential fatty acids in infantsinfants

Infants grow poorly and develop severe skin lesions if fed a diet lacking these acids.

Deficiency of essential fatty acids in Deficiency of essential fatty acids in adultsadults

A deficiency in adults can arise, however, after long-term intravenous feeding that contains inadequate essential fatty acids or among those surviving on limited and inadequate diets. Malnutrition in the developed world also results from many other causes; two common ones are unusual slimming diets and anorexia.

Waxes Waxes

Waxes; esters of long-chain alcohols with long-chain fatty acidsThe molecule has a weakly polar head group (the ester moiety) and a long, nonpolar tail (the hydrocarbon chains)Fatty acids found in waxes are usually saturatedThe alcohols may be saturated or unsaturated and may include sterols, such as cholesterolWaxes are water-insoluble due to the weakly polar nature of the ester group

ExampleExample

Triacontanylpalmitate: the main component of bee wax made from the esterification of palmitic acid (C16:0) to a C30 chain triacontanol (or melissyl alcohol).

TriglyceridesTriglycerides

In humans, fatty acids are stored as triacylglycerols in the cytoplasm of adipose cells (fat cells)Each triacylglycerol molecule is made of a glycerol molecule and three fatty acid chains

ExampleExample

The three fatty acids of any specific triacylglycerol are not necessarily the same.

Solid vs. liquid fatsSolid vs. liquid fats

Vegetable oils consist almost entirely of unsaturated fatty acids, whereas animal fats contain a much larger percentage of saturated fatty acids.

This is the primary reason for the different melting points of fats and oils

HydrogenationHydrogenation

The carbon carbon double bonds in vegetable oils can be hydrogenated to yield saturated fats in the same way that any alkene can react with hydrogen to yield an alkane.

Example: margarineExample: margarine

In margarine, only about two-thirds of the double bonds present in the starting vegetable oil are hydrogenated, so that the margarine remains soft in the refrigerator and melt on warm toast.

Trans fatTrans fat

Healthy fatty acids are unsaturated with cis configuration making them naturally in liquid form. The unhealthy animal fat is fully saturated and, therefore, solid.However, the saturated fat has better cooking properties.Therefore, chemists invented a method of converting unsaturated fat into solid form by partially hydrogenating it.In other words, partial hydrogenation converts some, but not all, double bonds into single bondsThis is called (trans fat), which has a better cooking properties and better taste.

Hydrogenation…partiallyHydrogenation…partially

The primary health risk identified for trans fat consumption is an elevated risk of coronary heart disease (CHD).

SoapSoap

Saponification: hydrolysis of fats and oils is by strong aqueous bases (NaOH or KOH) producing glycerol and three molecules of fatty acid carboxylate salts

How does soap work?How does soap work?

When mixed with water, the hydrophobic hydrocarbon tails cluster together to create a nonpolar microenvironment and the hydrophilic ionic heads interact with water. The resulting spherical clusters are called micelles.Grease and dirt are trapped in the center of the Micelles and the complex can be rinsed away.

ArachidonateArachidonate

Arachidonate is a 20-carbon fatty acid (eicosanoid). It is not found in plants, and can only be synthesized by mammals from linoleic acidIt is the major precursor of several classes of other molecules: prostaglandins, prostacyclins, thromboxanes, and leukotrienesThese are also called eicosanoids (from the Greek eikosi, "twenty") because they contain 20-carbon atoms

EicosanoidsEicosanoids

Functions of prostaglnadinsFunctions of prostaglnadins

lower blood pressureInfluence platelet aggregation during blood clottingstimulate uterine contractionslower gastric secretions

AspirinAspirin

Aspirin is anti-inflammatory and fever-reducing (antipyretic).It irreversibly inhibits cyclooxygenase (COX), the enzyme that catalyzes conversion of arachidonic acid to prostaglandins.

Aspirin and the heartAspirin and the heart

Aspirin inhibits platelet cyclooxygenase preventing platelet activation and aggregationAspirin acts as a potent antiplatelet agent by inhibiting generation of this mediator.

Targets of AspirinTargets of Aspirin

Cyclooxygenase is present in two forms in cells, COX-1 and COX-2. Aspririn targets both, but COX-2 should only be the target.Celebrex® is a Cox-2 inhibitor that is prescribed with a strong warning of side effects on the label.

Membrane lipidsMembrane lipids

The most prevalent class of lipids in membranes is the glycerophospholipids

PhospholipidsPhospholipids

Most phospholipids are similar to triacylglycerols in that their backbone is derived from glycerolTwo fatty acid chains are attached to carbons 1 and 2 and a phosphate group esterified to carbon 3The simplest phospholipids is phosphatidic acid (or phosphatidate) containing a hydrogen atom attached to phosphate

PhospholipidsPhospholipids

EmulsificationEmulsification

Because of their amphipathic nature, the act as emulsifying agents, that is substances that can surround nonpolar molecules and keep them in suspension in water

SphingolipidsSphingolipids

Sphingolipids are found in the plasma membranes of all eukaryotic cells and is highest in the cells of the central nervous systemThe core of sphingolipids is the long-chain amino alcohol, sphingosine

Amide bond

Types of sphingolipidsTypes of sphingolipids

The sphingolipids are divided into the two subcategories:

SphingomyelinsGlycosphingolipid (or glycolipids)

SphoingomyelinSphoingomyelin

Sphoingomyelin is a sphinglolipid that is a major component of the coating around nerve fibersThe group attached to C1 is a phosphocholine

GlycolipidsGlycolipids

Sphingolipids can also contain carbohydrates attached at C-1 and these are known as glycolipidsGlycolipids are present on cell membranes and act as cell surface receptors that can function in cell recognition (e.g., pathogens) and chemical messengers There are three types of glycolipids

CerebrosidesGlobosidesGangliosides

GlycolipidsGlycolipids

CerebrosidesCerebrosides

Cerebrosides, the simplest glycolipid, contain a single hexose (galactose or glucose)

Globosides and gangliosidesGlobosides and gangliosides

Globosides and gangliosides are more complex glycolipidsThe sugar residues include glucose, galactose, and N-acetylgalactosamine

Blood groupsBlood groups

There are 60 types of gangliosides and some of them are present on the surface of red blood cells giving the designations of blood types: A, B, AB, and O

SteroidsSteroids

Steroids have a "steroid nucleus" which is a fused four-ring system

CholesterolCholesterol

Cholesterol is the most abundant steroid, and is the precursor for all the other important steroids of mammalian metabolismIt is weakly amphipathic

Products of cholesterolProducts of cholesterol

Cholesterol is the precursor for many important hormones belonging to the steroid family such as sex hormonesIt is also the precursor of bile acids that is removed from the body in feces and is considered the only means of cholesterol removal from the bodySome vitamins such as vitamin D can be made starting from cholesterol

Vitamins A, D, E, and K are made from isoprenoids

Types of lipid structureTypes of lipid structure

Types of lipid structuresTypes of lipid structures1. Micelles1. Micelles

Amphipathic lipids self-assemble forming micelles (detergents) or bilayers (phospholipids)In micelles, the hydrophobic tails are buried and not exposed to H2O, whereas hydrophilic head groups are in contact with H2O

Types of lipid structuresTypes of lipid structures2. Bilayer2. Bilayer

Membrane lipids form bilayers

The hydrophobic effect provides the major driving force for the formation of these structures

Types of lipid structuresTypes of lipid structures3. Lipsomes3. Lipsomes

When phospholipids are shaken vigorously with water, they spontaneously form liposomes.Liposomes are potentially useful as carriers for drug delivery of hydrophilic drugs and DNA because liposomes can fuse with cell membranes and empty their contents into the cell.

Cell membranesCell membranes

Biological membranes contain lipids, proteins and carbohydratesExcept for specialized membranes, such as in mitochondria or myelin, the composition by weight is generally 45% lipid, 45% protein and 10% carbohydrateThe membrane is hypothesized in a model known as the fluid mosaic model

Fluid mosaic modelFluid mosaic modelfluid: not rigid mosaic: many componentsfluid: not rigid mosaic: many components

Extracellular

Intracellular

Membrane proteinsMembrane proteins

Peripheral proteins: are not inserted into the lipid bilayer but are associated with the exterior of membranes via noncovalent interactions with the hydrophobic tails, hydrophilic heads or other proteinsIntegral membrane proteins: anchored into membrane via hydrophobic regions once or several times. Some form channels.

GlycolipidsGlycolipids

The plasma membranes of animal cells also contain glycolipids and cholesterolThe glycolipids are found exclusively in the outer leaflet of the plasma membrane, with their carbohydrate portions exposed on the cell surface

Membrane is fluidicMembrane is fluidic

The fluidity of the membrane varies with the relative amounts of saturated and unsaturated fatty acids in the glycerophospholipids.The higher proportion of unsaturated fatty acid chains makes them not pack tightly together and the membrane remains fluidic.

Membrane is fluidicMembrane is fluidic

Because the bilayer membrane is fluid rather than rigid:

it is not easily rupturedproteins and lipids can move within the membranesmall nonpolar molecules can easily enter the cell through the membrane

Membrane permeabilityMembrane permeability

Small ions and polar molecules diffuse across the membrane via protein pores (simple diffusion) .Glucose and certain other substances (including amino acids) cross with the aid of proteins and without energy input (facilitated diffusion).Ions and other substances that maintain concentration gradients across the cell membrane cross with expenditure of energy and the aid of proteins (active transport).

Mechanisms of membrane transportMechanisms of membrane transport

Simple diffusionSimple diffusion

Small, nonpolar molecules, such as O2 and CO2 and and lipid-soluble substances, including steroid hormones, move through the hydrophobic lipid bilayer in this way.

Facilitated diffusionFacilitated diffusion

• Diffusion, facilitated diffusion is passive transport and requires no energy input.

• Solutes are helped across the membrane by proteins.

Active transportActive transport

• Solutes are transported across the membrane AGAINST the gradient (from low to high concentration).

• Energy from the conversion of ATP to ADP is used to change the shape of an integral membrane protein.